Perfusion heterogeneity of cerebral small vessel disease revealed via arterial spin labeling MRI and machine learning

Cerebral small vessel disease (CSVD) is associated with altered cerebral perfusion. However, global and regional cerebral blood flow (CBF) are highly heterogeneous across CSVD patients. The aim of this study was to identify subtypes of CSVD with different CBF patterns using an advanced machine learning approach. 121 CSVD patients and 53 healthy controls received arterial spin label MRI, T1 structural MRI and clinical measurements. Regional CBF were used to identify distinct perfusion subtypes of CSVD via a semi-supervised machine learning algorithm. Statistical analyses were used to explore alterations in CBF, clinical measures, gray and white matter volume between healthy controls and different subtypes of CSVD. Correlation analysis was used to assess the association between clinical measures and altered CBF in each CSVD subtype. Three subtypes of CSVD with distinct CBF patterns were found. Subtype 1 showed decreased CBF in the temporal lobe and increased CBF in the parietal and occipital lobe. Subtype 2 exhibited decreased CBF in the right hemisphere of the brain, and increased CBF in the left cerebrum. Subtype 3 demonstrated decreased CBF in the posterior part of the brain, and increased CBF in anterior part of the brain. The three subtypes also differed significantly in gender (p = 0.005), the proportion of subjects with lacune (p = 0.002), with periventricular white matter hyperintensity (p = 0.043), and CSVD burden score (p = 0.048). In subtype 3, it was found that widespread decreased CBF was correlated with total CSVD burden score (r = -0.324, p = 0.029). Compared with healthy controls, the three CSVD subtypes also showed distinct volumetric patterns of white matter. The current results associate different subtypes with different clinical and imaging phenotypes, which can improve the understanding of brain perfusion alterations of CSVD and can facilitate precision diagnosis of CSVD.